Abstract
Overuse and misuse of antibiotics leads to antibiotic resistance which has become a significant public health concern. Klebsiella pneumoniae is the most common pathogenic bacteria underlying nosocomial infections due to the expression of virulence factors and occurrence of antibiotic resistance. Evidence indicates that β-lactamase is involved in the antibiotic resistance of Klebsiella pneumoniae to β-lactam antibiotics. The aim of the present study was to investigate the association between the molecular biological mechanisms of antibiotic resistance of Klebsiella pneumoniae and extended-spectrum β-lactamase (ESBL). In order to assess temporal trends in prevalence and antimicrobial susceptibility, Klebsiella pneumoniae bacteria were isolated and the ESBL expression level was analyzed. Susceptibility tests were performed using automated systems. The β-lactam-resistance in Klebsiella pneumoniae was assessed by the β-lactam agar screen plate and respective MIC values were evaluated using E-test strips. The confirmatory disk diffusion methods were applied for phenotypic identification of the ESBL production of Klebsiella pneumoniae. The results showed that Klebsiella pneumoniae bacteria exhibited higher ESBL production after treatment with β-lactam compared to the control. The ESBL gene expression was upregulated in Klebsiella pneumoniae after treatment with β-lactam. Results identified that penicillin-binding proteins (PBPs) were associated with the growth and resistance to β-lactams. Zinc finger nuclease markedly inhibited the antibiotic resistance of Klebsiella pneumoniae to β-lactam. PBP knockdown abolished the inhibitory effects of zinc finger nuclease on the growth of Klebsiella pneumonia e induced by β-lactam antibiotic treatment. In conclusion, these results suggest that the resistance of Klebsiella pneumoniae bacteria to antimicrobial drugs is through the ESBL signaling pathway, which indicates that ESBL may be a potential target for abolishing resistance to β-lactam.